Transgenic mice bearing the LacZ gene, Muta (TM) mice, can be used to assess the in vivo mutagenic potency of chemicals. Heterocyclic amines (HAs) are potent mutagens found in cooked food which have shown to induce tumors in mice. By breeding the Muta (TM) mice with c-myc transgenic mice, the correlation between in vivo mutagenesis (as scored by mutations in LacZ), cell proliferation (as due to the presence of the oncogene), and onset of carcinogenesis due to initiation by heterocyclic amines can be determined. Preliminary studies show that the levels of HA-DNA adducts in the livers of c-myc/LacZ mice dosed with 2-amino-3- methylimidazo[4,5-f]quinoline (IQ) or 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx) were higher than the levels of HA-DNA adducts in the livers of C57bl/LacZ mice although there were no differences in the abilities of the two strains of mice to metabolically activate IQ to a mutagen in the Ames Salmonella mutagenicity assay. Thus suggesting that the presence of the c-myc transgene may be inhibiting the repair of HA-DNA adducts. We are currently examining the mutation frequencies in the livers of both c-myc/LacZ and C57bl/LacZ mice administered IQ, MeIQx and AalphaC. Studies in our laboratory have recently shown that c-myc transgenic mice develop dysplastic lesions of the liver that become carcinomas in the presence of phenobarbital. Although phenobarbital treatment caused an increase in the number of hyperplastic and dysplastic cells in the c-myc/LacZ mice compared to the C57bl/LacZ mice, there was no increase in the LacZ mutation frequency suggesting that phenobarbital is not genotoxic to these animals.